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Abstract This study aimed to register and analyse outcomes after iatrogenic ureteral injuries (IUI) with special emphasis on potential consequences of a delayed diagnosis, and further to analyse if the incidence of IUI has changed during the study period. 108 patients treated for an IUI during 2001–2021 were included. Injuries due to endourological procedures, planned tumour resection and traumatic injuries were excluded. All relevant information to answer the research questions were entered into a database. Chi-square and t-tests were used for categorical and continuous variables respectively. Regression analysis was used to evaluate potential change of incidence in IUIs over time. Our results showed that most IUIs (74, 69%) were caused by gynaecological surgery. 49 (45%) had a delayed diagnosis (not diagnosed intraoperatively). Younger age (mean 50 vs 62 years, p

Abstract Objectives The aim was to investigate the predictive abilities of a preoperative diffusion‐weighted MRI (dwMRI) among patients with surgically treated upper tract urothelial carcinoma (UTUC). Materials and methods Written consent was obtained from all participants in this prospective and ethically approved study. Thirty‐five UTUC patients treated with radical surgery were examined with a preoperative dwMRI and prospectively included during 2017–2022. Two radiologists examined the CT scans and dwMRIs for radiological stage, and the apparent diffusion coefficient (ADC) in the tumours at the dwMRI was registered. The radiologists were blinded for patient history, final histopathology and the readings of the other radiologist. The radiological variables were analysed regarding their abilities to predict muscle‐invasive disease (MID, T2–T4) and tumour grade at final pathology after radical surgery. The predictive abilities were assessed using chi‐square tests, Student's t‐test and calculating the area under the curve in a receiver operating characteristic (ROC) curve. Correlation between the two radiologists was quantified calculating the intra‐class correlation coefficient. P‐values

Background and objective: The adjustable transobturator male system (ATOMS) is an established treatment for patients with urinary incontinence after prostate surgery. Our objective was to evaluate the efficacy and the complication burdens associated with ATOMS with a focus on exploring the potential impact on previous radiotherapy (RT). Methods: We performed a retrospective analysis for consecutive patients who underwent ATOMS implantation procedure at a tertiary center over an 11-yr study period. Outcomes of interest were dryness at 3-mo follow up, postoperative complications (≤30 d), and late treatment failures (>30 d). Key findings and limitations: A total of 118 patients underwent ATOMS surgery performed by five different surgeons. Median follow-up was 67 mo (interquartile range 41–95). The mean 24-h pad count after surgery was 1.1 (range 0–8) and the mean reduction in pad weight was 179 g (range 0–1080). There was no significant difference in the reduction in pad use between groups with and without RT (−1.7 vs −2.4; p = 0.13). Multivariable analysis revealed that RT, degree of incontinence, and age were not risk factors for reoperation. Conclusions and clinical implications: ATOMS implantation is feasible in patients who have undergone prostate RT and patients with severe stress urinary incontinence after prostate surgery. We found that RT was not a risk factor for reoperation and there was no significant difference in pad weight reduction by RT status. This study offers new insight into potential incontinence surgery for male patients with stress urinary incontinence and previous RT. Patient summary: We assessed outcomes for patients who had an ATOMS (adjustable transobturator male system) device implanted to control stress urinary incontinence after prostate surgery. After implantation, 52.5% of the patients reported zero leakage and 39.9% reported only mild incontinence. Our results show that this device can improve continence after prostate surgery and is also suitable in patients who underwent radiotherapy.

Abstract Objectives The objective of this study was to evaluate adverse events and device events related to accessories used during ureteroscopy (URS). Materials and methods Analysis was performed of the records available in the Manufacturer and User Facility Device Experience database in the United States. Information was collected on characteristics of problem, timing, manufacturer verdict, successful completion of planned surgery, prolonged anaesthesia and injury to patient or staff. Results Five‐hundred seventy‐one events related to URS accessories were recorded. These were associated with the following devices: baskets (n = 347), access sheath (n = 86), guidewires (n = 78), balloon dilators (n = 27), ARDs (n = 17) and ureteral catheters (n = 16). Of the events, 12.7% resulted in patient injuries. Forty‐eight per cent of the events resulted in prolonged anaesthesia, but the planned surgery was successfully completed in 78.4% of all cases. Collectively, the manufacturers accepted responsibility due to actual device failure in only 0.5% of cases. Common problems for baskets were failure to deploy (39.5%) and complete detachment of basket head (34.6%) and partial breakage of the basket head (12.4%). Of the basket group, 4.3% required open or percutaneous surgery to remove stuck basket. Full break of the body of the access sheath occurred in 41.9% and complete ureteral avulsion in 3.5%. For balloon dilators, there was a burst in 37% of cases. Broken guidewires were associated with 11.5% requiring repeat intervention for retrieval and 6.4% required JJ stent due to perforation to the collecting system. No injuries to operating staff were recorded with accessory usage. Conclusion Accessories used during URS are fragile. Potential for serious injury does exist as a direct result of their use. Surgeons should familiarise themselves with these events and how they can be prevented.

Background: Both clinicians and patients use social media to post about health care issues such as kidney stone disease, but their perspectives may differ. Objective: To evaluate content and themes regarding kidney stone surgery shared by patients and urologists on Instagram. Design, setting, and participants: A search was performed on Instagram using the term “kidney stone surgery”. The first 100 posts from individuals who were clearly identified as a patient were assessed. We also assessed 100 posts from self-identified urologists. Outcome measurements and statistical analysis: A previously published system was applied as a framework for categorizing the information collected. Outcomes of interested included pain, recovery, and costs. Results and limitations: Some 71% of the patients were female and most of their posts (52%) were shared postoperatively. The most common themes covered in patient posts were the need for multiple operative sessions (45%), pain (43%), and recovery (42%). Other themes included activities of daily life (18%), return to work (11%), nervousness (16%), stent issues (31%), stent on a string (5%), diet and prevention (9%), gratitude for health care services (10%), disease recurrence (18%), and costs (10%). Some 94% of the urologists were male and their posts covered the following domains: recovery (11%), stent issues (3%), pain (1%), stent on a string (1%), gratitude for health care services (1%), and recurrence 1%. Among the posts from urologists, 79% included self-promotion and 52% covered new technology. Overall, 10% contained false information. The majority of the posts with surgical images had no clear statement regarding patient consent (97%). Conclusions: Kidney stone surgery can affect many areas of a patient’s quality of life. Most of the posts shared by patients were negative. Posts shared by urologists do not reflect the same themes. Moreover, there appears to be poor adherence to European Association of Urology recommendations regarding online professional conduct. Patient summary: Many patients use social media to share their experiences of kidney stone surgery. Posts are largely related to quality-of-life issues and are mostly negative. While urologists also use social media, the content they post on professional accounts is mostly focused on new technology and career promotion.

Abstract Introduction Single use ureteroscopes are a technological innovation that have become available in the past decade and gained increased popularity. To this end, there are now an increasing number of both benchside and clinical studies reporting outcomes associated with their use. Our aim was to deliver a narrative review in order to provide an overview of this new technology. Methods A narrative review was performed to gain overview of the history of the technology's development, equipment specifications and to highlight potential advantages and disadvantages. Results Findings from preclinical studies highlight potenial advantages in terms of the design of single use ureteroscopes such as the lower weight and more recent modifications such as pressure control. However, concerns regarding plastic waste and environmental impact still remain unanswered. Clinical studies reveal them to have a non inferior status for outcomes such as stone free rate. However, the volume of evidence, especially in terms of randomised trials remains limited. From a cost perspective, study conclusions are still conflicting and centres are recommended to perform their own micro cost analyses. Conclusions Most clinical outcomes for single use ureteroscopes currently match those achieved by reusable ureteroscopes but the data pool is still limited. Areas of continued debate include their environmental impact and cost efficiency.

Abstract Active angiogenesis may be assessed by immunohistochemistry using Nestin, a marker of newly formed vessels, combined with Ki67 for proliferating cells. Here, we studied microvascular proliferation by Nestin-Ki67 co-expression in prostate cancer, focusing on relations to quantitative imaging parameters from anatomically matched areas obtained by preoperative mpMRI, clinico-pathological features and prognosis. Tumour slides from 67 patients (radical prostatectomies) were stained for Nestin-Ki67. Proliferative microvessel density (pMVD) and presence of glomeruloid microvascular proliferation (GMP) were recorded. From mpMRI, forward volume transfer constant (Ktrans), reverse volume transfer constant (kep), volume of EES (ve), blood flow, and apparent diffusion coefficient (ADC) were obtained. High pMVD was associated with high blood flow (p = 0.008) and low ADC (p = 0.032). High Ktrans, kep, and blood flow were associated with high Gleason score. High pMVD, GMP, and low ADC were associated with most adverse clinico-pathological factors. Regarding prognosis, high pMVD, Ktrans, kep, and low ADC were associated with reduced biochemical recurrence-free- and metastasis-free survival (p ≤ 0.044) and high blood flow with reduced time to biochemical- and clinical recurrence (p

IntroductionThe aim of this study was to perform an evaluation of patient experiences and perceptions regarding kidney stone surgery on the social media platform TikTok. An increasing number of the public use social media (SoMe) as a platform to share their views regarding their experiences related to surgical treatment.MethodsUsing the hashtag #kidneystonesurgery, the 100 most recent video posts as of 01.01.2024 on TikTok were included. As well as demographic data such as gender and location, thematic content was also collected. To achieve this, a previously published framework was used and adapted for application in the setting of kidney stone surgery. This was piloted on 20 sample videos to assess its feasibility before revision and establishment of the final framework. This included the following key areas: Pain, Complications, Anxiety, Recovery, Return to work, Finances, Treatment delays, Diet and Prevention and stent complaints.ResultsThe majority of posts (95%) were from North America, 80% by females and the mean number of video views was 92,826 (range: 261–2,000,000). 76% of the videos discussed ureteroscopy (URS). 49% were filmed at the hospital, which was named in 9% of the videos. Top three topics discussed were: Recovery (65%), pain (62%) and stents (55%). This was followed by anxiety (39%) and complications (24%). 12% of these videos uploaded by lay people included basic medical information that was wholly incorrect. More than half of the posts (51%) were negative in tone. Treatment delays (5%) and a lack of sufficient preoperative information (4%) were also raised, that appeared to contribute to the negative reports. However, the main cause for negative tone owed to the 80% of the patients (n = 44) who discussed stents that focused their video on the pain suffered from the post operative stent.ConclusionThere is a high level of usership and engagement on TikTok on the subject of kidney stone surgery. The proportion of negative videos is high and much of this is related to the bothersome stent symptoms and complications. This could easily lead to misperceptions among potential patients about the true burden of such adverse events.

Male stress urinary incontinence is a debilitating condition, which can occur after prostate surgery. In persistent cases, surgery is indicated and a number of options are available. This includes one of the male slings, Adjustable transobturator male system (ATOMSTM, A.M.I, Austria). There are now an increasing number of studies published. This review provides an overview of the current status of this implant device including technical considerations, surgical outcomes and potential advantages and disadvantages compared to alternatives such as the artificial urinary sphincter.

Ureteroscopy is increasingly being used for urolithiasis. Technological innovations have been accompanied by wide variations in practice patterns. At the same time, a common finding in many studies, especially systematic reviews, is that the heterogeneity of outcome measurements and lack of standardisation can limit both the reproducibility and generalisability of study findings. While many checklists are available to improve study reporting, there are no ureteroscopy-specific ones. The Adult-Ureteroscopy (A-URS) checklist is a practical aid for both researchers and reviewers for studies in this field. It contains five main sections (study details, preoperative, operative, postoperative, and long term data) and a total of 20 items. Patient summary: We developed a checklist to improve how studies on ureteroscopy (insertion of a telescope through the urethra to inspect the urinary tract) in adults are reported. This could help in advancing the field and improving patient outcomes, as all the key information is captured.

Abstract Objectives The aim of this study is to evaluate the 2015 introduction of prebiopsy magnetic resonance imaging of the prostate (MRI‐P) as the standard of care for diagnosing prostate cancer (PCa) by the Norwegian public health care authorities. There were three specific objectives of this study: first, to evaluate the consequences of using different TNM manuals for clinical T‐staging (cT‐staging) in a national setting; second, to determine if the data reveals that MRI‐P based cT‐staging is superior to digital rectal examination (DRE)‐based cT‐staging compared with pathological T‐stage (pT‐stage) post radical prostatectomy; and third, to assess whether treatment allocations have changed over time. Materials and Methods All patients registered in the Norwegian Prostate Cancer Registry between 2004 and 2021 were retrieved and 5538 were eligible for inclusion. Concordance between clinical T‐stage (cT‐stage) and pT‐stage was assessed by percentage agreement, Cohen's kappa and Gwet's agreement. Results MR visualisation of lesions influences reporting of tumour extension beyond DRE findings. Agreement between cT‐stage and pT‐stage declined from 2004 to 2009, which coincided with an increase in the percentage being pT3. From 2010, agreement increased, which aligned with changes in cT‐staging and the introduction of MRI‐P. From 2017, regarding the reporting of cT‐DRE and cT‐Total (overall cT‐stage), agreement diminished for cT‐DRE but remained relatively stable (>60%) for cT‐Total. Regarding treatment allocation, the study suggests that staging with MRI‐P has shifted treatment towards radiotherapy in locally advanced high‐risk disease. Conclusion Introduction of MRI‐P has affected cT‐stage reporting. Agreement between cT‐stage and pT‐stage appears to have improved. This study suggests that use of MRI‐P influences treatment decisions in certain patient subgroups.

Background: Ureteroscopy (URS) in patients with urinary diversion is technically challenging. Common difficulties include anastomotic strictures, tortuosity, and failure to cannulate the ureteric orifice. There are few studies reporting outcomes in this special population. Objective: Our aim was to report outcomes at two tertiary centres in Europe. Design, setting, and participants: A multicentre retrospective cohort study was conducted between 2010 and 2022. Intervention: URS (antegrade and retrograde) procedures carried out in patients with urinary diversions. Outcome measurements and statistical analysis: Outcomes of interest included success at cannulating the ureteric orifice, stone-free rate (SFR), and complications. A logistic regression analysis was performed to identify potential predictors for success at cannulating the ureteric orifice and success at completing the intended procedure in a single session. Results and limitations: Fifty patients underwent 72 URS procedures, with most (86%) undergoing a retrograde approach. The majority (82%) of patients had undergone ileal conduit. Wallace was the commonest anastomosis type (64%). Ureteric anastomosis was cannulated successfully in 81% of cases. The most common reason for cannulation failure was the inability to identify the ureteric orifice (11%). A multivariable analysis revealed that an endourologist performing the case was associated with a significantly greater likelihood of cannulation success compared with consultants (odds ratio 25.9, p

Abstract. Background. The management of suspected kidney stone disease in pregnancy is challenging. In cases of persistent flank pain and where investigations may have rendered equivocal results, ureteroscopy (URS) is a recognized diagnostic and therapeutic intervention. This study aimed to investigate the safety and outcomes associated with performing URS during pregnancy, as the technique has evolved over the past 4 decades at our center. Materials and Methods. We performed a retrospective analysis of pregnant patients who underwent URS at our tertiary center between 1984 and 2022. Outcomes of interest included anesthetic approach, operative time, hospital stay, and complications. Results. Eighty-seven pregnant patients underwent 96 URS procedures, and 60% (n = 57) of these procedures were performed during the third trimester. Overall, 58% (n = 56) of the procedures were achieved with local anesthesia and light sedation. During the most recent decade, the latter was successfully carried out in 97% of the procedures, with the remainder occurring under spinal anesthesia as per patient choice. Overall, 57% (n = 50) of the whole study group had ureteral calculi found at the time of surgery and in 88% (n = 44) of these cases, fragmentation/extraction was performed. The remainder had insertion of ureteral stent with definitive clearance deferred until postpartum. Mean operative time and postprocedure hospital stay was 33 minutes (range, 7–100 minutes) and 2.2 days (range, 0–16 days), respectively. The overall intraoperative and postoperative complication rates were 2% and 11%, respectively. During the final decade, the latter improved to 6% and all adverse events were minor (Clavien I/II), with the exception of a single case. Regarding exit strategy, ureteral stent was placed in 42% (n = 40) of the procedures, 23% (n = 22) had ureteral catheter inserted, and the remainder (35%, n = 34) had none. Conclusions. Ureteroscopy can be safely performed during pregnancy using anesthetic approach with local anesthesia and light sedation. Development of a local protocol and multidisciplinary management algorithm are instrumental in enabling the delivery of such a service.

Ureteroscopy has become an increasingly popular surgical intervention for conditions such as urinary stone disease. As new technologies and techniques become available, debate regarding their proper use has risen. This includes the role of single use ureteroscopes, optimal laser for stone lithotripsy, basketing versus dusting, the impact of ureteral access sheath, the need for safety guidewire, fluoroscopy free URS, imaging and follow up practices are all areas which have generated a lot of debate. This review serves to evaluate each of these issues and provide a balanced conclusion to guide the clinician in their practice.

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n = 8) and non-progressing (NP) tumors (n = 16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. We identified 151 proteins, 1167 mRNAs and 63 miRNAs differentially expressed in P compared to NP low-risk tumors. Pathway analysis demonstrated overrepresentation of proteins related to “LXR/RXR and FXR/RXR Activation”, “Acute Phase Response Signaling” in NP compared to P samples. Integrating mRNA, miRNA and proteomic data, we developed a 10-component classifier including two proteins, three genes and five miRNAs, effectively differentiating P and NP ccRCC and capturing underlying biological differences, potentially useful to identify “low-risk” patients requiring closer surveillance and treatment adjustments. Key results were validated by immunohistochemistry, qPCR and data from publicly available databases. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients.

Abstract. Ureteroscopy during pregnancy has become increasingly recognized as a safe intervention. Performing it under local anesthesia and light sedation reduces the risks associated with general or regional anesthesia, such as difficult airway scenarios, hypothermia, and hypotension. In addition, this approach reduces the total amount of fetal exposure to medications and anesthetic agents. Performing ureteroscopy in this manner requires a number of adjustments and modifications to the standard technique. This article provides a summary in a step-by-step format, as well as an accompanying video demonstration.

While urolithiasis in children is rare, the global incidence is rising, and the volume of minimally invasive surgeries being performed reflects this. There have been many developments in the technology, which have supported the advancement of these interventions. However, innovation of this kind has also resulted in wide-ranging practice patterns and debate regarding how they should be best implemented. This is in addition to the extra challenges faced when treating stone disease in children where the patient population often has a higher number of comorbidities and for example, the need to avoid risk such as ionising exposure is higher. The overall result is a number of challenges and controversies surrounding many facets of paediatric stone surgery such as imaging choice, follow-up and different treatment options, for example, medical expulsive therapy, shockwave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy. This article provides an overview of the current status of paediatric stone surgery and discussion on the key topics of debate.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and one of the most common cancers. While survival for localized ccRCC is good, the survival of metastatic disease is not, and thirty percent of patients with ccRCC develop metastases during follow-up. Although current scoring methods accurately identify patients at low progression risk, a small subgroup of those patients still experience metastasis. We therefore aimed to identify ccRCC progression biomarkers in “low-risk” patients who were potentially eligible for adjuvant treatments or more intensive follow-up. Methods We assembled a cohort of ccRCC patients (n = 443) and identified all “low-risk” patients who later developed progressing tumors (n = 8). Subsequently, we performed genome-wide expression profiling from formalin-fixed samples obtained at initial surgery from these “low-risk” patients and 16 matched patients not progressing to recurrence with metastasis. The patients were matched for Leibovich sore, creatinine, age, sex, tumor size and tumor stage. Key results were confirmed with qPCR and external data from The Cancer Genome Atlas. Results Principal component analysis indicated that systematic transcriptomic differences were already detectable at the time of initial surgery. One thousand one hundred sixty-seven genes, mainly associated with cancer and immune-related pathways, were differentially expressed between progressors and nonprogressors. A search for a classifier revealed that overexpression of AGAP2-AS1, an antisense long noncoding RNA, correctly classified 23 of 24 samples, years (4.5 years average) in advance of the discovery of metastasis and without requiring larger gene panels. Subsequently, we confirmed AGAP2-AS1 gene overexpression by qPCR in the same samples (p

Introduction: Paediatric stone disease is rare in the Nordic communities. Still, the condition can require surgical intervention in the form of ureteroscopy (URS). Here, we report outcomes achieved at a regional (tertiary) centre. Patients and methods: Retrospective analysis was performed of consecutive patients (

Abstract The prognostic importance of transcription factors promoting epithelial–mesenchymal transition (EMT) and angiogenesis has not been well explored in prostate cancer patients with long follow‐up, nor the interplay between these factors. The objective of this study was to assess the individual protein expression and co‐expression of Twist, Slug (Snai2), Snail (Snai1), and hypoxia‐inducible factor‐1 alpha (Hif‐1α) in prostate cancer in relation to EMT, angiogenesis, hypoxia, tumour features, disease recurrence, and patient survival. Immunohistochemical staining was performed on tissue microarray sections from 338 radical prostatectomies with long follow‐up. In addition, 41 cases of prostatic hyperplasia, 33 non‐skeletal metastases, 13 skeletal metastases, and 33 castration‐resistant prostate carcinomas were included. Our findings were validated in external gene expression data sets. Twist was overexpressed in primary prostate cancer and markedly reduced in distant metastases (p

Bladder pain syndrome (BPS) is a prevalent and pervasive disease. The physical and psychological sequelae can be very burdensome for the patient, and the condition represents a real challenge for the clinician as well. With no simple pathognomonic test, finding harmony in navigating patient care can be demanding. Diagnosis and management rely upon a multidisciplinary and holistic approach. Treatment options include conservative measures and pharmacotherapies as well as bladder instillation therapies. Ultimately, surgery may be offered but only in cases of refractory disease. This article offers a pragmatic guide for clinicians managing this challenging disease.

Abstract Epithelial–mesenchymal transition (EMT) is important for tumour cell invasion and metastasis and is a feature of aggressive carcinomas. EMT is characterised by reduced E‐cadherin and increased N‐cadherin expression (EN‐switch), and increased expression of the EMT‐regulating transcription factor Forkhead box protein C2 (FOXC2) has been associated with progression and poor prognosis in various malignancies. FOXC2 was recently highlighted as a novel therapy target in prostate cancer, but survival data on FOXC2 are lacking. This study evaluates the expression of FOXC2, E‐cadherin and N‐cadherin in different prostatic tissues focusing on EMT, clinico‐pathological phenotype, recurrence and patient survival. Tissue microarray sections from 338 radical prostatectomies (1986–2007) with long and complete follow‐up, 33 castration resistant prostate cancers, 33 non‐skeletal metastases, 13 skeletal metastases and 41 prostatic hyperplasias were stained immunohistochemically for FOXC2, E‐cadherin and N‐cadherin. FOXC2 was strongly expressed in primary carcinomas, including castration resistant tumours and metastatic lesions as compared to benign prostatic hyperplasia. A hybrid epithelial–mesenchymal phenotype, with co‐expression of E‐cadherin and N‐cadherin, was found in the majority of skeletal metastases and in a substantial proportion of castration resistant tumours. In localised carcinomas, the EN‐switch was associated with adverse clinico‐pathological variables, such as extra‐prostatic extension, high pathological stage and lymph node infiltration. In univariate survival analyses of the clinically important, large subgroup of 199 patients with Gleason score 7, high FOXC2 expression and EN‐switching were significantly associated with shorter time to clinical recurrence, skeletal metastases and cancer specific death. In multivariate Cox' survival analysis, high FOXC2 and the EN‐switch, together with Gleason grade group (GG3 versus GG2), were independent predictors of time to these end‐points. High FOXC2 gene expression (mRNA) was also related to patient outcome, validating our immunohistochemical findings. FOXC2 and factors signifying EMT or its intermediate states may prove important as biomarkers for aggressive disease and are potential novel therapy targets in prostate cancer.

Abstract Background Transcriptome analysis is emerging as emerging as a promising tool to enhance precision of diagnosis and monitoring in solid organ transplantation. Clinical progress has however been hampered by the current reliance on samples from core needle biopsies. This proof-of-principle study examined whether fine needle aspirates, being less invasive, permit the ascertainment of the identical molecular information as core biopsies. Methods We collected fine needles aspirates from various needle sizes (G19, 21, 23, 25) and the corresponding core biopsies (G16 needle) of non-tumor tissue of full nephrectomy specimens from patients suffering from clear cell renal cell carcinoma (n = 11). RNA expression patterns of two gene sets (156 genes) were executed using targeted RNA sequencing in samples from fine needle vs. core needle samples. A subgroup of kidneys (n = 6) also underwent whole transcriptome RNA sequencing from core biopsies of tumor and peri-tumoral normal tissue (Tru Seq RNA Access, Illumina). Results Samples from all needle sizes except two G25 aspirates yielded RNA potentially suitable for sequencing of both gene sets. The mRNA expression patterns of the two gene sets were highly correlated between fine needle aspirates (G23) and corresponding (G16) core biopsies (r = 0.985 and 0.982, respectively). This close correlation was further documented by heat map, Principal Component Analyses (PCA) and whole transcription RNA sequencing. The similarity between fine neddle aspirates and core needle biopsies was additionally confirmed in the subgroup with complete RNA sequencing. Conclusions Fine needle biopsies yield similar genomic information to core needle biopsies. The less invasive nature of fine needle biopsies may therefore permit more frequent molecular monitoring and a more targeted use of core needle biopsies in native and especially in transplanted kidneys.

Abstract Background Sunitinib has become mainstay first line treatment for patients with metastatic renal clear cell carcinoma (mRCC). Still, useful predictive markers of response are lacking and urgently needed for clinical decision making. Methods In the present study we investigated the predictive value of standard serum markers as well as clinical markers, including C-reactive protein (CRP), Neutrophil to Lymphocyte ratio (NLR) and early hypertension (eHTN) in an unselected prospective patient population treated with sunitinib for mRCC. Forty-six patients were enrolled in a prospective single-arm study of predictive markers for sunitinib response. Response rates according to RECIST 1.1 were used as primary end-point. Secondary objectives were to evaluate prognostic value of the candidate markers with regard to progression free survival (PFS) and overall survival (OS). In addition, toxicity rates and quality of life was recorded. Results Median PFS and OS was 9.1 months and 15.0 months, respectively. Of 38 patients evaluable for response, 1 patient had complete response (CR), 7 had partial response (PR), 18 had stable disease (SD) and 12 had progressive disease (PD). Normal CRP at baseline was significantly associated with objective response (CR + PR) (p = 0.01). Normal CRP was also significantly associated with improved PFS and OS (Log rank, p = 0.05 and

High serum levels of the acute phase protein C-reactive protein (CRP) are associated with an adverse prognosis in renal cancer. The acute phase reaction is cytokine-driven and includes a wide range of inflammatory mediators. This overall profile of the response depends on the inducing event and can also differ between patients. We investigated an extended acute phase cytokine profile for 97 renal cancer patients. Initial studies showed that the serum CRP levels had an expected prognostic association together with tumor size, stage, nuclear grading, and Leibovich score. Interleukin (IL)6 family cytokines, IL1 subfamily mediators, and tumor necrosis factor (TNF)α can all be drivers of the acute phase response. Initial studies suggested that serum IL33Rα (the soluble IL33 receptor α chain) levels were also associated with prognosis, although the impact of IL33Rα is dependent on the overall cytokine profile, including seven IL6 family members (IL6, IL6Rα, gp130, IL27, IL31, CNTF, and OSM), two IL1 subfamily members (IL1RA and IL33Rα), and TNFα. We identified a patient subset characterized by particularly high levels of IL6, IL33Rα, and TNFα alongside an adverse prognosis. Thus, the acute phase cytokine reaction differs between renal cancer patients, and differences in the acute phase cytokine profile are associated with prognosis.

Patients with bladder cancer need frequent controls over long follow-up time due to high recurrence rate and risk of conversion to muscle invasive cancer with poor prognosis. We identified cancer-related molecular signatures in apparently healthy bladder in patients with subsequent muscular invasiveness during follow-up. Global proteomics of the normal tissue biopsies revealed specific proteome fingerprints in these patients prior to subsequent muscular invasiveness. In these presumed normal samples, we detected modulations of proteins previously associated with different cancer types. This study indicates that analyzing apparently healthy tissue of a cancer-invaded organ may suggest disease progression.

Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data obtained from FFPE kidney biopsies are comparable to data obtained from fresh stored material, thereby expanding the utility of archival tissue specimens.

Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. MicroRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. Core biopsies of both cancerous and adjacent normal tissues were obtained from patients (n = 12) undergoing nephrectomy. After small RNA-seq, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses. In a comparison of tumour vs. normal, 182 miRNAs were found with significant differential expression; miR-155 was of particular interest as it classified all ccRCC samples correctly and correlated well with tumour size (R2 = 0.83); miR-155 also predicted poor survival with hazard ratios of 2.58 and 1.81 in two different TCGA (The Cancer Genome Atlas) datasets in a univariate model. However, in a multivariate Cox regression analysis including age, sex, cancer stage and histological grade, miR-155 was not a statistically significant survival predictor. In conclusion, formalin-fixed paraffin-embedded biopsy tissues are a viable source of miRNA-sequencing material. Our results further support a role for miR-155 as a promising cancer classifier and potentially as a therapeutic target in ccRCC that merits further investigation.